1. Field of the Invention
The present invention is directed to an apparatus and a method for simultaneous reactions to produce a plurality of different chemical compounds and to effect a series of such simultaneous types of reactions sequential. It relies upon a multidimensional array of reaction vessels with liquid reaction mixtures and a separate array ofxe2x80x9cteabagsxe2x80x9d having fixed reactants located thereon. The invention relies upon shifting (changing) the combinations of fixed-reactant/liquid reaction mixtures to create a series of sequential groupings of different simultaneous reactants.
2. Information Disclosure Statement
The following prior art relates to methods and apparatuses for producing nifedipine type organic compounds and to methods of making a plurality of compounds:
U.S. Pat. No. 4,622,332 issued Nov. 11, 1986 to Egbert Wehinger et al. describes symmetric diesters of hantzsch dihydropyridines with hypotensive activity.
U.S. Pat. No. 4,631,211 issued Dec. 23, 1986 to Richard A. Houghten describes a means for carrying out sequential, solid phase syntheses which is disclosed as are methods of its use. The synthesis means comprises a foraminous container that encloses reactive particles. The particles are larger than any of the foraminae and have a known amount of covalently linked organic synthesis reactive functionality that is capable of reacting during the organic syntheses. The container and particles are substantially insoluble in water.
U.S. Pat. No. 4,665,081 issued May 12, 1987 to Kengo Doi et al. describes a new solid nifedipine preparation which comprises (a) a particulate dry composition having been obtained by subjecting nifedipine in mixture with casein and one or more inorganic excipients to co-pulverization or (b) a particulate dry composition having been obtained by adding an enteric high molecular substance and a plasticizer optionally with a higher fatty acid ester to the co-pulverized mixture obtained above, subjecting the mixture to co-pulverization and then dry-processing the co-pulverized product to a pharmaceutically acceptable solid form, as well as a process for preparing the solid composition (a) or (b) by the specific co-pulverization and a dry compounding method. The solid nifedipine preparation is excellent in dissolution of nifedipine or possesses a controlled dissolution rate of nifedipine. This preparation is useful as a vasodilating medicament for the dual purposes of rapid and gradual release of nifedipine from the preparation for the remedy of angina pectoris or hypertension.
U.S. Pat. No. 4,874,774 issued Oct. 17, 1989 to Koichi Ushimaru describes that nifedipine is formulated into a reactually administrable composition for administration to humans and animals to effect coronary dilation and for hypotensive effect.
U.S. Pat. No. 4,894,235 issued Jan. 16, 1990 to Hans Kohne describes an improved form of administration of 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridine-dicarboxylic acid-dimthylester (i.e., Nifedipine) is provided in which the Nifedipine is molecularly dispersed within a solidified melt of polyethylene glycols which are liquid, semi-solid and solid at room temperature. The weight ratio of liquid to non-liquid polyethylene glycols in the solidified melt ranges from about 7:23 to 23:7, the solidification temperature of the mixture ranges from about 25 degrees Celcius to 62 degrees Celcius and the mixture has a viscosity of from about 1 to 180,000 poise when measured at 20 degrees Celcius in admixture with up to about 40 percent by weight of water.
U.S. Pat. No. 5,264,446 issued Nov. 23, 1993 to Ahmed Hegasy describes the invention is directed to the provision of solid pharmaceutical compositions (and methods for their preparation) containing mifidipine crystals with a specific surface area of 1.0 to 4.0 m2/g., in admixture with a solid diluent. The said compositions overcome the deficiencies of prior art compositions containing nifidipine, which is known to have effect as a coronary vasodilator.
U.S. Pat. No. 5,463,564 issued Oct. 31, 1995 to Dimitris K. Agrafiotis describes a computer based, iterative process for generating chemical entities with defined physical, chemical and/or bioactive properties. During each iteration of the process, (1) a directed diversity chemical library is robotically generated in accordance with robotic synthesis instructions; (2) the compounds in the directed diversity chemical library are analyzed to identify compounds with the desired properties; (3) structure-property data are used to select compounds to be synthesized in the next iteration; and (4) new robotic synthesis instructions are automatically generated to control the synthesis of the directed diversity chemical library for the next iteration.
Notwithstanding the prior art, the present invention is neither taught nor rendered obvious thereby.
The present invention is an apparatus to provide a dynamic matrix system for synthesizing a plurality of chemical compounds simultaneously, i.e. in parallel, and to synthesize a series of plurality of simultaneously synthesized chemical compounds sequentially, i.e. in series. It includes a base support structure, a physical chemistry teabag support structure, a plurality of physical chemistry teabags and a fixed-reactant/liquid reactant mixture shifting (changing) means. The base support structure has a plurality of reaction vessels arranged in at least a two dimensional predetermined array, each of said reaction vessels having sufficient wall and bottom structure to support and contain a liquid reactant mixture, each of said reaction vessels adapted to receive physical chemistry teabags therein for chemical synthesis. The physical chemistry teabag support structure is adapted to hold and support a plurality of physical chemistry teabags arranged in at least a two dimensional predetermined teabag array, at least partially coinciding with said base support structure reaction vessel array. The plurality of physical chemistry teabags has at least one predetermined fixed reactant thereon. The fixed-reactant/liquid reactant mixture shifting means is adapted to alter specific fixed reactant-liquid reactant mixture combinations for at least a portion of said plurality of physical chemistry teabags relative to the liquid reactant mixture content of said plurality of reaction vessels. In various embodiments, the fixed-reactant/liquid reactant mixture shifting means could be a dynamic fluid/flow system, a mechanical movement means, or a combination of these. When the fixed reactant-liquid reactant mixture shifting means is a dynamic fluid flow system, each of plurality of reaction vessels includes at least one liquid channel connected thereto for filling and draining said plurality reaction vessels with a sequence of different liquid reactant mixture arrays of at least one liquid reactant mixture for each reaction vessel, and said apparatus further includes sufficient channel, valve and supply means for filling and draining said plurality of reaction vessels simultaneously and sequentially in accordance with the foregoing. When the fixed-reactant/liquid reactant mixture shifting means is a mechanical movement means it is functionally connected to at least one of said base support structure and said physical chemistry teabag support structure and is adapted to effect three dimensional movement between said base support structure and said physical chemistry teabag support structure so as to provide an in-out movement capability for simultaneous insertion, simultaneous hold and simultaneous removal motion of said plurality of physical chemistry teabags with said plurality of reaction vessels, and so as to provide relocation movement capability for simultaneous and sequential movement of said plurality of physical chemistry teabag so as to relocate a given physical chemistry teabag at least from a first reaction vessel to a second reaction vessel. In most preferred embodiments, the apparatus further includes temperature monitoring means and temperature adjustment means, said temperature adjusting means being selected from the group consisting of heating means, cooling means and combinations thereof These temperature adjustment means are functionally connected to each of the plurality of reaction vessels.
The invention also relates to a method for synthesizing a plurality of chemical compounds simultaneously and for synthesizing a plurality of chemical compounds simultaneously and to synthesize a series of plurality of simultaneously synthesized chemical compounds sequentially utilizing a dynamic matrix system. The method includes providing apparatus of the above-described types, and providing said plurality of reaction vessels with a plurality of different liquid reactant mixtures; operating said fixed-reactant/liquid reactant mixture shifting means so as to insert said plurality of physical chemistry teabags into said plurality of reaction vessels in a first position matrix for a sufficient holding time to create at least a first chemical compound synthesis; operating said fixed-reactant/liquid mixture shifting means so as to remove said plurality physical chemistry teabags from said plurality of reaction vessels; and, operating said fixed-reactant/liquid mixture shifting means so as to relocate at least one of said plurality of physical chemistry teabags relative to said plurality of reaction vessel and subsequently inserting said plurality of physical chemistry teabags into said plurality of reaction vessels in a second position matrix so that at least one of said physical chemistry teabags is positioned in a different reaction vessel from the reaction vessel of the first position matrix for a sufficient holding time to create at least a second chemical compound synthesis.